Arbuscular mycorrhizal (AM) symbiosis in vascular plant roots is an ancient mutualistic interaction that evolved with land plants. More recently evolved root mutualisms have recruited components of the AM signalling pathway as identified with molecular approaches in model legume research. Earlier we reported that the reduced mycorrhizal colonisation (rmc) mutation of tomato mapped to chromosome 8. Here we report additional functional characterisation of the rmc mutation using genotype grafts and proteomic and transcriptomic analyses. Our results led to identification of the precise genome location of the Rmc locus from which we identified the mutation by sequencing. The rmc phenotype results from a deletion that disrupts five predicted gene sequences, one of which has close sequence match to the CYCLOPS/IPD3 gene identified in legumes as an essential intracellular regulator of both AM and rhizobial symbioses. Identification of two other genes not located at the rmc locus but with altered expression in the rmc genotype is also described. Possible roles of the other four disrupted genes in the deleted region are discussed. Our results support the identification of CYCLOPS/IPD3 in legumes and rice as a key gene required for AM symbiosis. The extensive characterisation of rmc in comparison with its 'parent' 76R, which has a normal mycorrhizal phenotype, has validated these lines as an important comparative model for glasshouse and field studies of AM and non-mycorrhizal plants with respect to plant competition and microbial interactions with vascular plant roots.
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http://dx.doi.org/10.1007/s00572-013-0498-7 | DOI Listing |
Nucleic Acids Res
December 2024
Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Enzyme-mediated modifications of tRNA, such as 5-methylcytosine (m5C) installed by nuclear-enriched NOP2/Sun RNA methyltransferase 2 (NSUN2), play a critical role in neuronal development and function. However, our understanding of these modifications' spatial installation and biological functions remains incomplete. In this study, we demonstrate that a nucleoplasm-localized G679R NSUN2 mutant, linked to intellectual disability, diminishes NSUN2-mediated tRNA m5C in human cell lines and Drosophila.
View Article and Find Full Text PDFbioRxiv
November 2024
Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
Am J Respir Cell Mol Biol
November 2024
University of Pennsylvania Perelman School of Medicine, Medicine, Philadelphia, Pennsylvania, United States.
Nat Commun
September 2024
Oncogene Biology Laboratory, Francis Crick Institute, London, UK.
Mutant selective drugs targeting the inactive, GDP-bound form of KRAS have been approved for use in lung cancer, but resistance develops rapidly. Here we use an inhibitor, (RMC-4998) that targets RAS in its active, GTP-bound form, to treat KRAS mutant lung cancer in various immune competent mouse models. RAS pathway reactivation after RMC-4998 treatment could be delayed using combined treatment with a SHP2 inhibitor, which not only impacts tumour cell RAS signalling but also remodels the tumour microenvironment to be less immunosuppressive.
View Article and Find Full Text PDFNat Commun
August 2024
Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino, Torino, Italy.
Selective KRAS inhibitors have been developed to covalently lock the oncogene in the inactive GDP-bound state. Two of these molecules, sotorasib and adagrasib, are approved for the treatment of adult patients with KRAS-mutated previously treated advanced non-small cell lung cancer. Drug treatment imposes selective pressures leading to the outgrowth of drug-resistant variants.
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